The main purpose of this proposed research project is the further investigation of the determinants of host cell resistance to the multiplication of certain bacteria within mammalian cells. We have recently found that interferon preparations and Poly I.C, an inducer of interferon, inhibit the intracellular growth of Shigella flexneri, Type 2a in cell cultures. Other bacteria such as N. gonorrhea and various mycobacteria have been also shown to multiply in cell cultures. The in vitro multiplication of bacteria in tissue cultures provides an excellent experimental model for examining the host cell's resistance to bacterial infection. We plan to explore the exact nature of the observed inhibition of intracellular bacterial growth by interferon and also extend our studies to experimental animal model bacterial infections such as shigella infection of rabbit conjunctiva and of the gastrointestinal tract. A better understanding of the factors involved in the "virulence" of intracellular bacteria and host cell susceptibility may eventually lead to a new approach to controlling these infections.